The Role of Peptide-Based Tumor Vaccines on Cytokines of Adaptive Immunity: A Review

International Journal of Peptide Research and Therapeutics - Recently, peptide-based materials have been applied to solving many therapeutic problems and have shown particular efficacy as cancer...     

The Study of the Altering Substrate Refractive Index on Single Symmetry Split-Ring Resonator Unit Cell Metamaterial

Plasmonics - This study employed single symmetry split-ring resonator (SRR) to implement biosensor applications. The behavior of the applied mechanism was observed comprehensively by altering the...     

The Prooxidant Action of Dietary Antioxidants Leading to Cellular DNA Breakage and Anticancer Effects: Implications for Chemotherapeutic Action Against Cancer

Plant-derived dietary antioxidants have attracted considerable interest in recent past for their ability to induce apoptosis and regression of tumors in animal models. While it is believed that the antioxidant properties of these agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, it could not account for apoptosis induction and chemotherapeutic observations. In this article, we show that dietary antioxidants can alternatively switch to a prooxidant action in the presence of transition metals such as copper. Such a prooxidant action leads to strand breaks in cellular DNA and growth inhibition in cancer cells. Further, the cellular DNA breakage and anticancer effects were found to be significantly enhanced in the presence of copper ions. Moreover, inhibition of antioxidant-induced DNA strand breaks and oxidative stress by Cu(I)-specific chelators bathocuproine and neocuproine demonstrated the role of endogenous copper in the induction of the prooxidant mechanism. Since it is well established that tissue, cellular, and serum copper levels are considerably elevated in various malignancies, such a prooxidant cytotoxic mechanism better explains the anticancer activity of dietary antioxidants against cancer cells.     

Suitability indices and habitat suitability index model of Caspian kutum (Rutilus frisii kutum) in the southern Caspian Sea

The relationship between species and habitat is important in ecosystem-based fisheries management. Habitat suitability index (HSI) modeling is a valuable tool in ecology and can be used to describe the relationship between fish abundance and ecological variables in order to estimate the suitability of specific habitats. In the present study, an HSI model was applied to determine suitable habitats for the Caspian kutum (Rutilus frisii kutum), an important commercial species in the southern Caspian Sea. An arithmetic mean model (AMM) was found to be the most appropriate model for describing the relationship between two of the environmental variables investigated (depth and benthos biomass). However, a geometric mean model explained the evident relationship when all four environmental variables were used (depth, benthos biomass, photosynthetically active radiation and sea surface temperature). The areas with an HSI > 0.5 had over 85 % of the total catch indicating the reliability of the prediction of the Caspian kutum habitat using the AMM. The present study showed that depth and substrate structure are the most important environmental variables for the Caspian kutum to select its habitats, and between remotely sensed data, chlorophyll a, photosynthetically active radiation and sea surface temperature are the most critical parameters for near real-time prediction of the Caspian kutum habitat.     

Improved Activity of a Thermophilic Cellulase,Cel5A,from Thermotoga maritima on Ionic Liquid Pretreated Switchgrass

Ionic liquid pretreatment of biomass has been shown to greatly reduce the recalcitrance of lignocellulosic biomass, resulting in improved sugar yields after enzymatic saccharification. However, even under these improved saccharification conditions the cost of enzymes still represents a significant proportion of the total cost of producing sugars and ultimately fuels from lignocellulosic biomass. Much of the high cost of enzymes is due to the low catalytic efficiency and stability of lignocellulolytic enzymes, especially cellulases, under conditions that include high temperatures and the presence of residual pretreatment chemicals, such as acids, organic solvents, bases, or ionic liquids. Improving the efficiency of the saccharification process on ionic liquid pretreated biomass will facilitate reduced enzyme loading and cost. Thermophilic cellulases have been shown to be stable and active in ionic liquids but their activity is typically at lower levels. Cel5A_Tma, a thermophilic endoglucanase from Thermotoga maritima, is highly active on cellulosic substrates and is stable in ionic liquid environments. Here, our motivation was to engineer mutants of Cel5A_Tma with higher activity on 1-ethyl-3-methylimidazolium acetate ([C₂mim][OAc]) pretreated biomass. We developed a robotic platform to screen a random mutagenesis library of Cel5A_Tma. Twelve mutants with 25–42% improvement in specific activity on carboxymethyl cellulose and up to 30% improvement on ionic-liquid pretreated switchgrass were successfully isolated and characterized from a library of twenty thousand variants. Interestingly, most of the mutations in the improved variants are located distally to the active site on the protein surface and are not directly involved with substrate binding.     

DegS and RseP Homologous Proteases Are Involved in Singlet Oxygen Dependent Activation of RpoE in Rhodobacter sphaeroides

Singlet oxygen (¹O₂) is the main agent of photooxidative stress and is generated by photosensitizers as (bacterio)chlorophylls. It leads to the damage of cellular macromolecules and therefore photosynthetic organisms have to mount an adaptive response to ¹O₂ formation. A major player of the photooxidative stress response in Rhodobacter sphaeroides is the alternative sigma factor RpoE, which is inactivated under non-stress conditions by its cognate anti-sigma factor ChrR. By using random mutagenesis we identified RSP_1090 to be required for full activation of the RpoE response under ¹O₂ stress, but not under organic peroxide stress. In this study we show that both RSP_1090 and RSP_1091 are required for full resistance towards ¹O₂. Moreover, we revealed that the DegS and RseP homologs RSP_3242 and RSP_2710 contribute to ¹O₂ resistance and promote ChrR proteolysis. The RpoE signaling pathway in R. sphaeroides is therefore highly similar to that of Escherichia coli, although very different anti-sigma factors control RpoE activity. Based on the acquired results, the current model for RpoE activation in response to ¹O₂ exposure in R. sphaeroides was extended.     

Nitrogen fertiliser and establishment method affect growth,yield and nitrogen use efficiency of rice under alternate wetting and drying irrigation

Sustainable rice production through selection of best suitable cultivar, water-efficient crop establishment method and optimum nitrogen (N) management practice is needed to feed the growing world population. Two polyhouse experiments were conducted to evaluate the response of rice to different rates and schedules of N application under different establishment methods subjected to alternate wetting and drying (AWD) irrigation. In the first experiment, the response of two rice cultivars (Pathumthani 1, RD57) under three establishment methods (transplanting [TP], wet direct seeding [WDS], dry direct seeding [DDS]) and five N rates (0 [N₀], 30 [N₃₀], 60 [N₆₀], 90 [N₉₀], 120 [N₁₂₀] kg ha⁻¹) was evaluated. The second experiment consisted of the same cultivars and establishment methods, but with four N application schedules (T₁: 100% at basal; T₂: 75% + 25% at basal and at active tillering, respectively; T₃: 50% + 25% + 25% at basal, at active tillering and at panicle initiation, respectively; and T₄: 25% + 25% + 25% + 25% each at basal, at active tillering, at panicle initiation and at early flowering or just before heading starts) applied at the rate of N₆₀ kg ha⁻¹. Plants were maintained under AWD irrigation (soil was saturated by applying water whenever soil water potential drops to −5 kPa during the implementation period) in both experiments. RD57 performed better than Pathumthani 1 having higher shoot dry matter, panicle number, grain yield, total N uptake and apparent N recovery efficiency. TP gave better response than WDS and DDS regardless of cultivars. Application of N₁₂₀ resulted in better growth, yield and its components and total N uptake regardless of establishment methods and cultivars. Increasing N rate decreased N use efficiency (NUE). Scheduling the interval of N application to two or three times (T₂ or T₃) for RD57 and Pathumthani 1, respectively, provided overall better results, and could be recommended for the tested rice cultivars. An optimal N rate and selection of critical growth stages for N application would be very effective for maximising yield and NUE under the water-saving cultivation technique of AWD irrigation.     

Structure and Stability Analysis of Cytotoxic Complex of Camel α-Lactalbumin and Unsaturated Fatty Acids Produced at High Temperature

Abstract

α-Lactalbumin (α-La), together with oleic acid can be converted to a complex, which kills tumor cells selectively. Cytotoxic α-La -oleic acid and a-La -linoleic acid complexes were generated by adding fatty acid to camel holo a-La at 60°C (referred to as La-OA-60 and La-LA-60 state, respectively). Structural properties of these complexes were studied and compared to the camel α-La. The experimental results show that linoleic acid induces a-La partial unfolding but oleic acid does not change the protein structure significantly. Also the stability of La-OA-60 and La- LA-60 toward thermal denaturation was measured. The order of temperature at the transition midpoint is as follows: La-LA-60 < La-0A-60 < α-La. La-0A-60 complex inhibited tubulin polymerization in vitro. Although the structures of La-0A-60 and La-LA-60 were different, these two complexes had similar cytotoxic effect to DU145 human prostate cancer cells. Samples of La-0A-60 that have been renatured after denaturation lost the specific biological activity toward tumor cells.     

Anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors with sub-micromolar potency in the cell-based replicon assay

Optimization efforts on the anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors 1 and 2 resulted in the identification of multiple structural elements that contributed to improved cell culture potency. The additive effect of these elements resulted in compound 46, an inhibitor with enzymatic (IC₅₀) and cell culture (EC₅₀) potencies of less than 100 nanomolar.     

Design,synthesis and biological evaluation of novel aminothiazoles as antiviral compounds acting against human rhinovirus

We describe here the design, synthesis and biological evaluation of antiviral compounds acting against human rhinovirus (HRV). A series of aminothiazoles demonstrated pan-activity against the HRV genotypes screened and productive structure–activity relationships. A comprehensive investigational library was designed and performed allowing the identification of potent compounds with lower molecular weight and improved ADME profile. 31d-1, 31d-2, 31f showed good exposures in CD-1 mice. The mechanism of action was discovered to be a host target: the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIIIß). The identification of the pan-HRV active compound 31f combined with a structurally distinct literature compound T-00127-HEV1 allowed the assessment of target related tolerability of inhibiting this kinase for a short period of time in order to prevent HRV replication.